Objective:To study the clinical manifestations and genetic characteristics of neonatal-onset primary mitochondrial disease (PMD) caused by nuclear gene mutations.Methods:From May 2020 to March 2022, the clinical data, genetic results and follow-up information of neonates with PMD admitted to the Department of Neonatology of our two hospitals were retrospectively analyzed.Results:A total of 4 patients were enrolled, all with hyperlactatemia and metabolic acidosis. In case 1, the fetal cranial MRI showed agenesis of corpus callosum. In case 2, echocardiography after birth indicated hypertrophic cardiomyopathy. Whole exome sequencing found the following mutations: EARS2 nuclear gene c.1294C>T and c.971G>T variants, COA6 nuclear gene c.411_412insAAAG variant, ACAD9 nuclear gene c.1278+1G>A and c.895A>T variants, FOXRED1 nuclear gene c.1054C>T and c.3dup variants. Mitochondrial second-generation sequencing and multiplex ligation-dependent probe amplification showed no abnormalities. Cases 1 and 3 died during the neonatal period. Case 2 died at 2-year-and-2-month of age. Case 4 was followed up to 1 year of age with developmental delay.Conclusions:The main phenotypes of neonatal-onset PMD caused by nuclear gene mutations are hyperlactatemia, refractory metabolic acidosis and cardiomyopathy, which have a poor prognosis. Proactive genetic tests are helpful for early diagnosis.

Objective To investigate the serum levels of miR-665 and miR-144 in the elderly pa-tients with chronic heart failure(CHF)and their relationship with cardiac function.Methods A total of 120 elderly CHF patients who were diagnosed and treated in our hospital from March 2021 to March 2023 were collected and then divided into NYHA grade Ⅱ(n=39),Ⅲ(n=51)and Ⅳ(n=30)subgroups according to the results of NYHA classification.Another 120 elderly healthy volunteers during the same period were recruited as the control group.Clinical data and cardiac function indicators were collected,and the expression levels of miR-665 and miR-144 in se-rum were detected.Pearson correlation analysis was applied to analyze the relationship of miR-665 and miR-144 levels with cardiac function indicators.Results The CHF group had significantly de-creased LVEF,increased left ventricular end-diastolic diameter(LVEDD)and left ventricular end-systolic diameter(LVESD),and elevated serum levels of miR-665 and miR-144 than the control group(P＜0.01).Sequentially reduced LVEF and raised LVEDD and LVESD values and serum miR-665 and miR-144 levels were observed in the patients with NYHA grades Ⅱ,Ⅲ,and Ⅳ in turn(P＜0.01).Pearson correlation analysis showed that there was a positive correlation of the serum level of miR-665 with that of miR-144 in CHF patients(r=0.693,P=0.000),of the miR-665 and miR-144 levels with LVEDD(r=0.485,r=0.507,P＜0.01)and LVESD(r=0.539,r=0.494,P＜0.01),and a negative correlation of the serum levels with LVEF(r=-0.577,r=-0.591,P＜0.01).Conclusion The serum levels of miR-665 and miR-144 are elevated in elderly CHF patients,and are closely associated with their cardiac function.

ObjectiveTo research the mechanism underlying the effect of raw and processed Aurantii Fructus Immaturus switched to Zhishi Shaoyaosan （ZSS） on constipation-predominant irritable bowel syndrome （C-IBS） rats via the brain-gut-microbiota axis. MethodEighty rats were randomly divided into the blank， model， positive drug （pinaverium bromide， 15.625 mg·kg^-1）， raw ZSS， stir-fried ZSS， bran-fried ZSS， charcoal-fried ZSS and finished ZSS groups （3.75 g·kg^-1）， with 10 rats in each group. Except for the blank group， which received intragastric administration of 0.9% sodium chloride solution at room temperature， all other groups were administered the ice solution at 0 to 4 ℃ （2 mL·d^-1， for a total of 14 d） to establish the C-IBS rat model. The fecal water content and the propulsion rate of small intestine were detected after 14 d of continuous drug administration. The levels of 5-hydroxytryptamine （5-HT）， vasoactive intestinal peptide （VIP）， neuro-peptide Y （NPY）， calcitonin gene-related peptide （CGRP）， substance P （SP）， diamine oxidase （DAO） and D-lactic acid （D-LA） were detected by enzyme linked immunosorbent assay （ELISA）. Hematoxylin-eosin （HE） staining was used to observe the changes in colonic pathological injury in each group. The expression levels of cyclic adenosine monophosphate （cAMP）， protein kinase A （PKA） and aquaporin-3 （AQP3） mRNA in colon tissues were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and the protein expressions of VIP and AQP3 in colon tissues were detected by Western blot. The content of short chain fatty acids （SCFAs） was determined by gas chromatography-mass spectrometry. ResultCompared with the blank group， the fecal water content and intestinal propulsion rate of rat in the model group were significantly decreased （P<0.01）， and the levels of 5-HT， VIP， CGRP and SP in serum were significantly increased. Simultaneously， the NPY levels significantly decreased （P<0.01）， the levels of DAO and D-LA in plasma were significantly increased （P<0.01）， and the mucosal epithelium of colon tissue was slightly damaged， with reduced goblet cells and significantly reduced luminal granules. The mRNA expression levels of AQP3， cAMP and PKA and the protein expression levels of AQP3 and VIP in colon tissue were significantly decreased （P<0.05， P<0.01）. The total amount of SCFAs in feces showed an obvious decreasing trend， with the contents of acetic acid， isobutyric acid， isovaleric acid， valeric acid and caproic acid decreased significantly， while the contents of propionic acid and butyric acid increased significantly （P<0.05， P<0.01）. Compared with the model group， the treatment groups increased the intestinal propulsion rate， improved the intestinal mucosal barrier function， and adjusted the level of serum brain-gut peptide in C-IBS rats （P<0.05， P<0.01）. The expression levels of AQP3， cAMP， PKA mRNA and VIP， AQP3 protein in colon tissue of rats in all treatment groups were increased. All the treatment groups had a significant downregulation of the content of SCFAs except for isobutyric acid in rat feces， and the effect of ZSS prepared by the bran-fried Aurantii Fructus Immaturus was superior than that of other ZSS. ConclusionThe raw and processed Aurantii Fructus Immaturus switched to ZSS could influence the brain-gut-microbiota axis to treat C-IBS rats and it is more reasonable to use bran-fried Aurantii Fructus Immaturus in ZSS.

Background Patients with schizophrenia of Yangming Fushi syndrome experience more severe symptoms,and a substantial proportion of patients derive inadequate benefit from antipsychotics and suffer from serious adverse effects,yet few studies have been conducted on the treatment of schizophrenia of Yangming Fushi syndrome with Zengye Chengqi decoction.Objective To explore the efficacy of Zengye Chengqi decoction combined with olanzapine in the treatment of schizophrenia of Yangming Fushi syndrome,in order to provide references for the treatment of schizophrenia with the combination of traditional Chinese and western medicine.Methods A total of 60 patients attending the Second Affiliated Hospital of Xinxiang Medical College from January 2022 to August 2023 and fulfilling the International Classification of Diseases(ICD-10)diagnostic criteria for schizophrenia were enrolled,and assigned into study group(n=30)and control group(n=30)using random number table methods.All patients were treated with olanzapine,and study group was given Zengye Chengqi decoction on this basis.Treatment for both groups lasted for 4 weeks.All participants were assessed using Positive and Negative Syndrome Scale(PANSS),Montreal Cognitive Assessment(MoCA)and Event-Related Potential P300 at baseline and end of treatment.The occurrence of adverse reactions was recorded at the end of treatment.Results Study group reported a higher treatment effective rate compared with control group(χ2=9.320,P=0.002).After treatment,study group detected a significant reduction in PANSS subscales and total scores(F=10.287,8.258,8.844,20.079,P<0.01),and a notable increase in scores of delayed recall and orientation domains from MoCA(F=4.463,22.255,P<0.05 or 0.01)when compared with control group,with statistical difference.For the P3 component of event-related potential,study group produced significantly larger amplitudes than control group(F=4.247,P<0.05).The incidence rate of abnormal liver function,constipation and increased body mass index(BMI)in study group was lower than those in control group(χ2=4.320,4.463,7.200,P<0.05 or 0.01).Conclusion Zengye Chengqi decoction combined with olanzapine are found to be effective in improving the psychotic symptoms and cognitive function and alleviating the adverse reactions of patients with schizophrenia of Yangming Fushi syndrome.

Objective:To study the epidemic characteristics of scrub typhus in Yantai City from 2006 to 2022, and provide a scientific basis for prevention and control of scrub typhus in Yantai City.Methods:In the subsystem "Infectious Disease Monitoring System" of the "China Disease Prevention and Control Information System", data on the outbreak of scrub typhus in Yantai City from January 1, 2006 to December 31, 2022 were collected and processed using software such as SPSS 23.0 for descriptive statistics.Results:A total of 599 scrub typhus cases were reported in Yantai City from 2006 to 2022, with an average annual reported incidence of 0.51/100 000. The reported incidence showed an upward trend year by year from 2006 to 2014 (χ 2trend = 144.72, P < 0.001), and reached a peak in 2014 (1.04/100 000). There was another small peak in 2019 (0.91/100 000). The incidence of scrub typhus showed a clear seasonal unimodal distribution, with October being the peak, accounting for 72.62% (435/599). In addition to Changdao County, other 12 cities (districts) reported scrub typhus cases. The top 3 cities with average annual reported incidence were Zhaoyuan City (1.58/100 000), Laizhou City (1.47/100 000) and Laiyang City (0.75/100 000). In all reported cases, the male to female ratio was 1.00∶1.07 (289∶310). The cases were mainly concentrated in the age range of 50 to 79, accounting for 74.46% (446/599). There was a statistically significant difference in the number of patients in different age groups in different years ( H = 38.71, P = 0.001). Farmers accounted for 88.65% (531/599) of the affected population. Conclusions:The incidence of scrub typhus in Yantai City shows an increasing trend and is widely distributed. It is recommended to strengthen the diagnosis, monitoring and infection management of scrub typhus.

Background Occupational pneumoconiosis is the most common occupational disease in Qinghai Province and China. From the perspective of public health, it is important to assess the disease burden using disability-adjusted life years (DALY) and economic losses. Objective To evaluate the disease burden of occupational pneumoconiosis in Qinghai Province, and to provide a basis for the formulation and implementation of relevant prevention and control strategies. Methods Based on the registered data, a database of occupational pneumoconiosis cases confirmed and reported in Qinghai Province was established. The survival status and death dateof occupational pneumoconiosis patients from 2015 to 2019 were confirmed by on-site visit, telephone survey, matching search of Death Information Registration and Management System, and consulting other departments. The life loss due to occupational pneumoconiosis from 2015 to 2019 was assessed using DALY as an indicator and data from the Global Burden of Disease 2019 (GBD 2019) study. Inpatients with officially diagnosed occupational pneumoconiosis from a hospital in Qinghai Province in 2019 were selected as study subjects, the direct economic loss was evaluated with hospitalization expenses, and the indirect economic loss due to occupational pneumoconiosis in Qinghai Province in 2019 was calculated by human capital approach. Results From 2015 to 2019, 505 new cases of occupational pneumoconiosis were reported in Qinghai Province, and there were 348 death cases. Prevalent cases and years lost due to disability (YLD) due to occupational pneumoconiosis were increased, while DALY and years of life lost (YLL) due to occupational pneumoconiosis decreased firstly and then increased. In each year, there were 87% or more of the DALY, YLL, or YLD attributed to silicosis and coal workers' pneumoconiosis. In 2019, the occupational pneumoconiosis-associated DALY was 2173.55 person years. The total hospitalization expense incurred by 42 inpatients with occupational pneumoconiosis was 1256345.19 yuan. The total hospitalization expense and average daily cost of the inpatients with stageⅡand Ⅲ pneumoconiosis were higher than that of the inpatients with stageⅠ (P<0.05), and the hospitalization expense was higher in the ≥60 years age group than in the <60 years age group (P<0.05). In 2019, the indirect economic burden incurred by occupational pneumoconiosis in Qinghai Province was 44108581.65 yuan, and accounted for 0.15‰ of the gross domestic product (GDP) of the province. Conclusion The disease burden associated with occupational pneumoconiosis in Qinghai Province are outstanding. Silicosis and coal workers' pneumoconiosis are the key contributors. Targeted intervention measures including dust hazard control, enterprise management, follow-up and rehabilitation management of pneumoconiosis should be taken to prevent and control the occurrence and progression of pneumoconiosis and alleviate disease burden of pneumoconiosis.

Sleep deprivation (SD) has a profound impact on the central nervous system, resulting in an array of mood disorders, including depression and anxiety. Despite this, the dynamic alterations in neuronal activity during sleep deprivation have not been extensively investigated. While some researchers propose that sleep deprivation diminishes neuronal activity, thereby leading to depression. Others argue that short-term sleep deprivation enhances neuronal activity and dendritic spine density, potentially yielding antidepressant effects. In this study, a two-photon microscope was utilized to examine the calcium transients of anterior cingulate cortex (ACC) neurons in awake SD mice in vivo at 24-hour intervals. It was observed that SD reduced the frequency and amplitude of Ca2+ transients while increasing the proportions of inactive neurons. Following the cessation of sleep deprivation, neuronal calcium transients demonstrated a gradual recovery. Moreover, whole-cell patch-clamp recordings revealed a significant decrease in the frequency of spontaneous excitatory post-synaptic current (sEPSC) after SD. The investigation also assessed several oxidative stress parameters, finding that sleep deprivation substantially elevated the level of malondialdehyde (MDA), while simultaneously decreasing the expression of Nuclear Factor erythroid 2-Related Factor 2 (Nrf2) and activities of Superoxide dismutase (SOD) in the ACC. Importantly, the administration of gallic acid (GA) notably mitigated the decline of calcium transients in ACC neurons. GA was also shown to alleviate oxidative stress in the brain and improve cognitive impairment caused by sleep deprivation. These findings indicate that the calcium transients of ACC neurons experience a continuous decline during sleep deprivation, a process that is reversible. GA may serve as a potential candidate agent for the prevention and treatment of cognitive impairment induced by sleep deprivation.

Objective: To investigate whether differences exist in attention deficit hyperactivity disorder (ADHD) and intelligence between children born by cesarean delivery and those born by vaginal delivery. Methods: This retrospective study included singleton children that were born between January 2013 and December 2014. The Chinese version of the Conners’ Parent Rating Scale–Revised (CPRS-48) was required on the probability of psychological and behavioral problems. The China–Wechsler Intelligence Scale for Children (C-WIRS) was used for evaluation of crystallized intelligence and Raven’s Standard Progressive Matrices for evaluation of fluid intelligence. Results: A total of 10,568 valid questionnaires were obtained. CPRS-48 ADHD index and detection rate were higher in cesarean delivery group than those in vaginal delivery group. Cesarean delivery groups had a lower performance intelligence quotient score according to C-WISC. Conclusion Children born by cesarean delivery were more likely to have a risk of ADHD and a lower performance intelligence quotient compared with those born by vaginal delivery.

Objective: This study’s objective is to assess the efficacy and safety of Pulsed Magnetic Therapy System (PMTS) in improving insomnia disorder. Methods: Participants with insomnia disorder were randomly assigned to receive either PMTS or sham treatment for four weeks (n= 153; PMTS: 76, sham: 77). Primary outcomes are the Insomnia Severity Index (ISI) scores at week 0 (baseline), 1, 2, 3, 4 (treatment), and 5 (follow-up). Secondary outcomes are the Pittsburgh Sleep Quality Index at baseline and week 4, and weekly sleep diary-derived values for sleep latency, sleep efficiency, real sleep time, waking after sleep onset, and sleep duration. Results: The ISI scores of the PMTS group and the sham group were 7.13±0.50, 11.07±0.51 at week 4, respectively. There was a significant group×time interaction for ISI (F3.214, 485.271=24.25, p<0.001, ηp 2=0.138). Only the PMTS group experienced continuous improvement throughout the study; in contrast, the sham group only experienced a modest improvement after the first week of therapy. At the end of the treatment and one week after it, the response of the PMTS group were 69.7% (95% confidence interval [CI]: 58.6%–79.0%), 75.0% (95% CI: 64.1%–83.4%), respectively, which were higher than the response of the sham group (p<0.001). For each of the secondary outcomes, similar group×time interactions were discovered. The effects of the treatment persisted for at least a week. Conclusion PMTS is safe and effective in improving insomnia disorders.

Thiamine responsive megaloblastic anemia syndrome is a rare autosomal recessive disease caused by mutations of the SLC19A2 gene that encodes the high-affinity thiamine transporter-1.Thiamine responsive megaloblastic anemia syndrome involves extensive organs and systems with various clinical manifestations.The typical triad is megaloblastic anemia, non-autoimmune diabetes, and sensorineural deafness.The diagnosis of thiamine responsive megaloblastic anemia syndrome depends on the detection of the pathogenic gene SLC19A2.Thiamine replacement therapy is the first-line treatment.Blood glucose of patients with thiamine responsive megaloblastic anemia syndrome should be comprehensively managed, and hearing aids and cochlear implants can be used to improve the hearing.